Several types of therapeutic treatments for cancer in humans are in current, common use. These treatments include surgery, x-rays or radiation from radioactive sources and chemotherapy, these treatments being often combined in various ways to enhance treatment effectiveness.
Although such conventional treatment techniques have been successful in treating cancer in many patients and in prolonging the lives of many other patients, they are not only frequently ineffective against many types of cancer, but very often, if not usually, have severely adverse side effects at the necessary treatment levels. Protracted treatment of cancer patients by x-rays or chemotherapy, as an illustration, tends to eventually destroy or inhibit the patients' natural immunological systems to an extent that many patients eventually succumb to common infectuous diseases, such as influenza or pneumonia, which otherwise probably would not be fatal. Also, many patients having advanced stages of cancer or complications may become too weak to withstand the trauma of surgical or other cancer treatments; hence, the treatments cannot be undertaken or must be discontinued.
Due both to the prevalence and the typically severe consequences of human cancer, as well as frequent ineffectiveness of current treatments such as those mentioned above, medical researchers are continually experimenting to attempt to discover and develop improved or alternative cancer treatment methods with their associated treatment apparatus.
For centuries, hyperthermia, that is, artifically elevated body temperature, has been known to be quite effective in treating many types of bodily disorders, duplicating, in effect, the body's own fever defense mechanism. More recently, hyperthermia has become an important area of research into its possible use and effectiveness, either alone or in combination with more conventional cancer treatments, in treating cancer in humans. This research is important in that hyperthermia techniques appear to have the potential of being extremely effective for treating many or most types of human cancers, without the often severely adverse side effects associated with current cancer treatments.
Researchers into hyperthermia treatment of cancer have commonly reportedly that many types of malignant growths in humans can be thermally destroyed, usually with no seriously adverse side effects, by heating the malignancies to temperatures slightly below that injurious to most normal, healthy cells. Furthermore, many types of malignant cell masses have reportedly been found to have substantially poorer than normal heat transfer or dissipation characteristics, presumably due to poorer vascularity and reduced blood flow characteristics. Consequently, these types of growths appear capable of preferential hyperthermia treatment. Poorly vascular malignant growths, as a result, can reportedly be heated to temperatures several degrees higher than that which immediate surrounding healthy tissue reaches. This promises to enable hyperthermic treatment of those types of malignant growths which are no more thermally sensitive than normal tissue without destruction of normal cells, and additionally to enable higher temperature, shorter hyperthermia treatment times of more thermally sensitive types of malignancies which exhibit poor vascularity, usually an advantage for important medical reasons.
In this regard, researchers have commonly reported that as a consequence of these thermal characteristics of most malignant growths and the thermal sensitivity of normal body cells, hyperthermia temperatures for treatment of human cancer should be carefully limited within a relatively narrow effective and safe temperature range. Below a threshold temperature of about 41.5.degree. C. (106.7.degree. F.), significant thermal destruction of most malignant growths of cells has normally not been found to occur. At lower hyperthermic temperatures, undesirable growth of many types of malignancies, to the contrary, is believed to be stimulated.
At slightly higher hyperthermic temperatures, in or above the approximate range of 43.degree. C. to 45.degree. C. (109.4.degree. F. to 113.degree. F.), thermal damage to most types of normal cells is routinely observed; thus, great care must be taken not to exceed these temperatures in healthy tissue. Exposure duration at any elevated temperature is, of course, an important factor in establishing extent of thermal damage to healthy tissue. However, if large or critical regions of the human body are heated into, or above the 43.degree. C. to 45.degree. C. range, for even relatively short times, serious permanent injury or death may be expected to result. As an example, in a book entitled "Recent Results in Cancer Research, Selective Heat Sensitivity of Cancer Cells", edited by A. Rossi-Fanelli et al, published by Springer-Verlug; Berlin, Heidelberg, New York, 1977, experimental observations on thermal sensitivity of malignant growths and cells are discussed, observed thermal death times being characterized as a straight line on a time vs temperature, semi-logarithm plot (at Page 97).
Various common types of skin or near surface cancers in humans have frequently been found to respond favorably to treatment by direct application of surface heat, for example, by hot fluid baths which cause surface hyperthermia at the applied region. However, more deeply located malignant growths, principally due to characteristic blood flow heat transferring properties of intervening healthy tissue, cannot reliably be heated to a destructive temperature by surface heating, without probability of causing, at the same time, excessive damage to the overlying healthy tissue.
A non-surface heating technique involving artifically inducing a high body fever in the patient by exposure to a contageous disease, has sometimes in the past been used, but has seldom been satisfactory because of the difficulty in maintaining the fever in the permissible hyperthermia treatment range and the danger to the patient, from the disease itself, when the fever is permitted to remain at necessary high temperature levels. Alternatively, whole body heated blood perfusion hyperthermia techniques have also generally been unsatisfactory, due to the slowness of the treatment and trauma to the patient.
Because of these and other deficiencies in pre-existing hyperthermia techniques for treating cancer in humans, possibility of using highly penetrating electromagnetic radiation (EMR) to induce biological hyperthermia in living tissue is currently under serious investigation as an attractive alternative, particularly for hyperthermic treatment of deeply located and/or widely metasticized malignant growths, but also for surface or near-surface malignancies.
Historically, alternating electric currents, at frequencies above about 10 KHz, were found late in the last century to penetrate and cause heating in biological tissue. As a result, high frequency electric currents, usually in the megahertz frequency range, have since been widely used for therapeutic treatment of such common bodily disorders as infected tissue and muscle injuries. Early in this century, the name "diathermia" was given to this EMR tissue heating technique, and several discrete EMR frequencies in the megahertz range have subsequently been allocated spedifically for diathermy use in this country by the Federal Administration Commission (FCC).
Experimental therapeutic treatment of malignant growths in living tissue by high frequency EMR induced hyperthermia has been reported at least as early as 1933. For example, in an article by Dr. J. W. Schereschewsky entitled "Biological Effects of Very High Frequency Electromagnetic Radiation", published in RADIOLOGY, April, 1933, curative or inhibitory effects of EMR hyperthermia on mice tumors, at EMR frequencies up to 400 MHz, was described. A summary of research in the EMR hyperthermia field was also presented by Schereschewsky. More recently, for example, researchers Guy, Lehman and Stonebridge in 1974 summarized the background of high frequency EMR medical hyperthermia research and discussed then current experimental activity in the field, in their article entitled "Therapeutic Application of Electromagnetic Power", appearing in the PROCEEDINGS OF THE IEEE, Volume 62, No. 1, in January, 1974.
A number of even more current discussions relating to EMR hyperthermia treatment of cancer may, for example, be found in a compilation of articles on the subject published in the book "Cancer Therapy by Hyperthermia and Radiation", edited by Christian Streffer et al and published by Urban and Schwarzenberg; Baltimore, Munich 1978.
In spite of there having been reported encouraging and often apparently successful medical results obtained by using EMR induced hyperthermia to treat malignant growths in humans, the treatments have normally been of an experimental nature, typically being used on cancer patients otherwise considered incurable or terminal, since serious problems relating to hyperthermic damage to healthy tissue have commonly been encountered. As with conventional surface heating, these healthy tissue damage problems are particularly associated with thermally destroying malignant growths deeply located in, or close to, thermally sensitive tissue.
This unintended EMR thermal damage of healthy tissue can typically be attributed to design and use of existing EMR irradiating apparatus, rather than to any basic deficiency in the concept of EMR hyperthermia treatment. EMR apparatus used, for example, often radiate excessive and/or improperly controlled EMR heating fields. A further disadvantage is that the specific diathermy allocated frequencies which are ordinarily used are typically non-optimum radiating frequencies for deep penetration. In addition, existing EMR hyperthermia apparatus and techniques tend to increase incidence and severity of thermal "hot spotting" in healthy tissue, as may be caused by constructive interference of applied energy waves, either by characteristic reflections at interfaces between different types of tissue, or by simultaneous use of more than one EMR applicator.
To overcome these and other problems associated with heretofore available EMR hyperthermia apparatus used for medical research or other medical purposes, applicant has disclosed improved EMR hyperthermia apparatus in U.S. patent applications, Ser. No. 002,584, now U.S. Pat. No. 4,271,848, and Ser. No. 048,515, now U.S. Pat. No. 4,341,227, filed on Jan. 11, 1979 and June 14, 1979, respectively. In these two patent applications, parallel plate and waveguide-type EMR applicators, together with associated EMR systems, were described and claimed, the applicators being particularly adapted for irradiating biological tissue or tissue simulating matter from outside the tissue. Emphasis was placed on broad band EMR capabilities, enabling, for example, research definition of important parameters associated with hyperthermic treatment of malignancies in humans. Also described in such patent applications was simultaneous operation of two (or more) applicators arranged to improve deep tissue heating characteristics.
In applicant's subsequent U.S. patent application, Ser. No. 050,050, filed on June 19, 1979, now abandoned needle-type, invasive EMR applicators, for enabling EMR hyperthermia in sub-surface tissue regions, were described. By surrounding, with a phased array of these invasive applicators, a localized tissue region, such as a region containing a malignant growth, substantially uniform heating of the surrounded region by constructive interferences of the sychronous EMR fields was described.
However, there still exists an important need for EMR hyperthermia apparatus capable of causing uniform deep EMR heating of thick tissue masses, such as trunk and thigh portions of an adult human body, in which large or widely dispersed malignant growths may be found. For these and similar regions of the body, an encircling annular EMR applicator apparatus, which may comprise an array of smaller applicators, is ordinarily prefered so that EMR energy is emitted inwardly from all around the enclosed body region to be EMR heated.
To this end, large annular magnetic coils have been used to radiate a magnetic field into a body region disposed through the coil. Although such radiated magnetic fields are known to penetrate deeply in human tissue, uniform heating across the encircled tissue region is still difficult to achieve. This is because a decreasingly smaller volume of tissue is presented for magnetic field coupling as the center of the encircled tissue region is approached. Thus, when such annular magnetic coils are used to cause hyperthermia in biological tissue, surface tissue regions can be expected to be heated much more than underlying central tissue regions.
Similar thermal gradients appear to result from heretofore available annular EMR applicators, which have typically been constructed from a number of individual applicators of types used for local EMR heating. Although some improvements in deeper heating can ordinarily be expected from positioning, and operating in unison, a number of individual EMR applicators around a tissue region, the necessary uniformity of tissue heating can ordinarily only be expected with heretofore ignored specific design consideration relating to tissue characteristics and radiating aperture configuration.
Considering the above cited narrow, effective and safe thermal treatment range of only about 4.degree. C., necessity for a low thermal gradient across the encircled tissue can be seen as necessary if all types of malignant growths are to be capable of successful treatment by hyperthermia techniques. Consequently, uniformity of specimen heating should be a very important design objective of EMR apparatus.
When, however, success in thermally treating deeply located malignant growths by heretofore available types of annular applicator apparatus have been experienced, the results appear to be more attributable to poorer heat dissipation properties of large malignant growths than to the desirable uniformity of heating. Heating uniformity, not heretofore available, would also enable effective thermal treatment, for example, of deeply located, widely dispersed, small groups of malignant cells in early stages of growth before the associated reduced heat transfer characteristics become significant. Ability to provide at least substantially uniform heating of encircled tissue regions is also very important, for example, in areas of EMR hyperthermia research into hyperthermic effects on normal healthy tissue.
In addition to the difficult medical related problems associated with non-uniform EMR tissue heating, heretofore available annular applicators typically have other problems. As an example, because of poor impedance matching with the tissue region being irradiated, most available apparatus are narrow band apparatus and usually require power from the source to be much greater than that actually radiated into the tissue specimen. This requires the apparatus to be substantially more expensive than would otherwise be necessary, not only because of the usually much greater cost of a higher power EMR source, but also because of specially required tuning devices and high temperature resistant components in which the lost power is converted to heat. Also the amount of stray radiation leakage also tends to be increased, such impedance mismatched EMR apparatus thereby requiring expensive EMR shielding to prevent possible radiation danger for operators of the apparatus.
For these and other reasons, applicant has invented annular EMR applicator apparatus, and corresponding methods for EMR irradiation, which provide greatly improved uniformity of EMR heating in an encircled region of biological tissue or tissue simulating matter. Applicant's improved annular applicator apparatus provides such heating uniformity for whatever purposes the EMR heating may be required or desired, whether or not these purposes relate to medical hyperthermic treatment of cancer or of other bodily disorders and diseases or to other areas of medical research.